Ob jec ti ve: Levosimendan is a relatively new inotropic agent. Unlike other inotropic agents, Levosimendan does not increase cellular calcium intake, so that, does not cause intracellular calcium overload and related arrhythmias. Atrial fibrillation (AF) was shown to be an independent risk factor for mortality and morbidity in large heart failure (HF) trials. Heart failure induces AF, AF aggravates HF and therefore they generally coexist. We conducted a study to investigate if there is any differential effect of Levosimendan in HF patients with chronic AF and without AF. Methods: This is a prospective study. Consecutive patients, who were hospitalized because of acutely decompensated HF due to systolic dysfunction and decided Levosimendan administration, were enrolled. Patients were classified into two as those with AF (group A) and those with sinus rhythm (control group, group S). All patients had echocardiography before and after administration. Echocardiographic data were evaluated by ANOVA repeated measurements test. Results: Baseline left ventricle ejection fraction (LVEF) was poorer in group with AF (mean LVEF for group A: 20.9%, for group S: 26.4%, p=0.04). Baseline diastolic parameters were equally impaired. After infusion, diastolic parameters like velocity of propagation (Vp) and isovolumic relaxation time (IVRT) improved almost to same extent in both groups but deceleration time (DT) did not. IVRT values decreased (p=0.012) both in group S (from 108.6±23.2 msec to 100.4±28.4 msec) and group A (from 117.3±25.1 msec to 92.0±20.9 msec) without a significant difference between groups (p=0.180 for interaction). Another valuable diastolic parameter, Vp was also similarly improved (p<0.01) in both groups to similar extent (for group A, from 35.4±8.8 cm/sec to 41.1±7.7 cm/sec, for group S, from 33.7±7.5 cm/sec to 37.8±7.6 cm/sec; p=0.498 for interaction). Conclusion: We have shown that in patients with chronic HF and AF, levosimendan improves left ventricular systolic and diastolic functions as good as those with HF and sinus rhythm. We suggest that a positive electrophysiological effect of levosimendan on failing myocardial tissue seems to fill the absence of atrial booster in patients with AF who are on beta-blocker therapy.